US11529506B2 - System and method for ultrasonic bladder therapeutic agent delivery - Google Patents
System and method for ultrasonic bladder therapeutic agent delivery Download PDFInfo
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- US11529506B2 US11529506B2 US17/044,184 US201917044184A US11529506B2 US 11529506 B2 US11529506 B2 US 11529506B2 US 201917044184 A US201917044184 A US 201917044184A US 11529506 B2 US11529506 B2 US 11529506B2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
- A61M25/1011—Multiple balloon catheters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0092—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N7/00—Ultrasound therapy
- A61N7/02—Localised ultrasound hyperthermia
- A61N7/022—Localised ultrasound hyperthermia intracavitary
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
- A61M2025/1043—Balloon catheters with special features or adapted for special applications
- A61M2025/105—Balloon catheters with special features or adapted for special applications having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
- A61M2025/1043—Balloon catheters with special features or adapted for special applications
- A61M2025/1052—Balloon catheters with special features or adapted for special applications for temporarily occluding a vessel for isolating a sector
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
- A61M2025/1043—Balloon catheters with special features or adapted for special applications
- A61M2025/1059—Balloon catheters with special features or adapted for special applications having different inflatable sections mainly depending on the response to the inflation pressure, e.g. due to different material properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
- A61M2025/1043—Balloon catheters with special features or adapted for special applications
- A61M2025/1093—Balloon catheters with special features or adapted for special applications having particular tip characteristics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2210/00—Anatomical parts of the body
- A61M2210/10—Trunk
- A61M2210/1078—Urinary tract
- A61M2210/1085—Bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N7/00—Ultrasound therapy
- A61N2007/0039—Ultrasound therapy using microbubbles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N7/00—Ultrasound therapy
- A61N2007/0043—Ultrasound therapy intra-cavitary
Definitions
- the present invention in some embodiments thereof, relates to a catheter for bladder therapeutic agent delivery and, more particularly, but not exclusively, to an ultrasonic-driven bladder therapeutic agent delivery.
- Intravesical therapy of the urinary bladder involves the bladder inner surface which is covered with transitional epithelium lining called urothelium, and glycosaminoglycans (GAG) units found on the urothelium. Both the urothelium and the GAG units may function as an important barrier to toxins and waste found in the urine, giving the bladder wall its low permeability characteristic. However, this compact and tight barrier may also restrict effective penetration of therapeutic agents delivered into the bladder during intravesical treatments. Some therapeutic molecules may not penetrate the bladder barrier at all.
- Ultrasound cavitation is a mechanism by which acoustic waves can increase tissue permeability. Cavitation bubbles collapse on the tissues with high energy and open up pores in the tissues, which result in the increased permeability of the tissues to therapeutic agents.
- a catheter for ultrasonic-driven bladder therapeutic agent delivery includes: a tube, two or more expandable portions mounted on the tube, one or more ultrasound transducers mounted on the tube between the two or more expandable portions, and a transducer sleeve disposed between the two or more expandable portions and accommodating the one or more transducers.
- the transducer sleeve and the expandable portions include a single balloon.
- the expandable portion comprises a stent.
- the maximal cross-sectional area of the transducer sleeve at an expanded state is smaller than the maximal cross-sectional area of any one of the expandable portions at least at their greatest circumference.
- at least one of the expandable portions is spheroid and at least one of the expandable portions and the tube are concentric.
- at least one of the expandable portions and the transducer are concentric.
- the tube includes at least one fluid port located within a lumen of at least one of the expandable portions and/or at least one fluid port along its length that opens to a lumen of a bladder.
- the port is configured to supply fluid into the lumen of the bladder and/or evacuate fluid out of the bladder.
- the transducer is elevated from a surface of the tube so that to define a gap between the transducer and the surface of the tube.
- the greatest circumference of the transducer sleeve is less than 50% of the greatest circumference of at least one expandable portion and/or the inflation pressure of the transducer sleeve is greater than the inflation pressure of the expandable portions.
- the tube includes one or more conduits that supply therapeutic fluid via the port.
- the tube includes one or more conduits that supply gassed fluid via the port.
- the tube includes one or more conduits that supply fluid via the port.
- the transducer is configured to form cavitations in the gassed therapeutic fluid.
- a catheter for ultrasonic-driven bladder therapeutic agent delivery the catheter includes a tube, having a proximal portion and a distal end, a proximal expandable portion mounted on the proximal portion of the tube, one or more transducers mounted on the tube between the proximal expandable portion and the distal end, and a transducer sleeve between the proximal expandable portion and the distal end accommodating the one or more transducers.
- one or more of the expandable portions comprises a balloon.
- the balloon is toroidal and/or configured to inflate distally towards the distal end.
- the tube includes at least one fluid port along its length that opens to a lumen of a bladder and/or is located between the transducer and the balloon.
- the port is configured to supply fluid into the lumen of the bladder and/or evacuate fluid out of the bladder.
- the greatest circumference of the transducer sleeve is less than 50% of the greatest circumference of the balloon.
- a volume is defined between the transducers and the transducer sleeve.
- the inflation pressure of the transducer sleeve is greater than the inflation pressure of the balloon.
- the tube includes one or more conduits that supply therapeutic fluid via the port.
- a method for treating a bladder using a catheter for ultrasonic-driven bladder therapeutic agent delivery including: inserting a distal expandable portion of the catheter into the bladder via a urethra, expanding the expandable portion, supplying therapeutic fluid into the bladder through at least one therapeutic fluid port in the catheter, advancing the catheter in the bladder and inserting a proximal expandable portion of the catheter into the bladder, expanding the proximal expandable portion and trapping the therapeutic fluid between the distal expandable portion and the proximal expandable portion, and applying ultrasound to form cavitation in the therapeutic fluid.
- the method for treating a bladder using a catheter for ultrasonic-driven bladder therapeutic agent delivery comprises supplying of therapeutic fluid into the bladder through at least one therapeutic fluid port in the catheter after stopping to emit ultrasound energy.
- the method includes supplying the therapeutic fluid through a port between the expandable portions.
- the therapeutic fluid is gaseous therapeutic fluid.
- a method for treating a bladder using a catheter for ultrasonic-driven bladder therapeutic agent delivery including: inserting a distal expandable portion of the catheter into the bladder via a urethra, expanding the expandable portion, supplying gassed fluid into the bladder through at least one fluid port in the catheter, emitting ultrasound energy and forming cavitations in the gassed fluid, draining the bladder content, supplying therapeutic fluid into the bladder through at least one therapeutic fluid port in the catheter, and emitting ultrasound energy and forming cavitations in the therapeutic fluid.
- the method includes draining and flushing the bladder with saline prior to supplying the gassed fluid into the bladder.
- the method includes stopping emitting ultrasound energy during the draining of the bladder content and/or the supplying of the therapeutic fluid into the bladder through at least one therapeutic fluid port in the catheter.
- a catheter for ultrasonic-driven bladder therapeutic agent delivery including: a tube having a proximal expandable portion and a distal end; and at least one transducer sleeve accommodating at least one ultrasound transducer mounted on the tube between the proximal expandable portion and the distal end.
- a catheter wherein at least one expandable portion is expandable inside a bladder from a contracted state to an expanded state at which the expandable portion is urged against the bladder wall to form a sealed volume within the bladder between the expandable portion and a trigone area of said bladder.
- the catheter includes at least one additional expandable portion, wherein the transducer sleeve is disposed between the proximal and said at least one additional expandable portion.
- the transducer sleeve and at least one of the expandable portions are in fluid communication.
- the maximal cross-sectional area of the transducer sleeve at an expanded state is smaller than the maximal cross-sectional area of any one of the expandable portions at least at their greatest circumference.
- at least one of the expandable portions is spheroid.
- At least one of the expandable portions and the tube are concentric. In some embodiments, at least one of the expandable portions and the transducer are concentric. In some embodiments, the tube comprises at least one fluid port located within a lumen of at least one of the expandable portions.
- the tube comprises at least two fluid ports in fluid communication with the lumen of the transducer sleeve and wherein fluid flow is maintained between the ports.
- the transducer is positioned between the ports.
- the tube comprises at least one therapeutic fluid port along its length that opens to a lumen of a bladder.
- the catheter includes a blind tip at the distal end, wherein the at least one therapeutic fluid port is positioned along the circumference of the tip.
- the transducer is elevated from a surface of the tube so that to define a gap between the transducer and the surface of the tube.
- the catheter comprises at least one spacer positioned on the tube and wherein the transducer is mounted on the at least one spacer.
- the greatest circumference of the transducer sleeve is less than 50% of the greatest circumference of at least one expandable portion.
- the tube comprises one or more conduits that supply fluid via said therapeutic fluid port.
- At least one expandable portion is toroidal. In some embodiments, at least one expandable portion is configured to inflate distally towards the distal end. In some embodiments, the catheter comprises at least one fluid port located between the transducer and at least one expandable portion.
- an expanded state a volume is defined between the transducer and the transducer sleeve.
- a method for treating a bladder using a catheter for ultrasonic-driven bladder therapeutic agent delivery including: inserting a distal expandable portion of the catheter into the bladder via a urethra, expanding the expandable portion, supplying therapeutic fluid into the bladder through at least one therapeutic fluid port in the catheter, advancing the catheter in the bladder and inserting a proximal expandable portion of the catheter into the bladder, expanding the proximal expandable portion and trapping the therapeutic fluid between the distal expandable portion and the proximal expandable portion, and forming cavitations in the therapeutic fluid.
- the method includes supplying the therapeutic fluid through a port between the expandable portions.
- the therapeutic fluid is gaseous therapeutic fluid.
- a method for treating a bladder using a catheter for ultrasonic-driven bladder therapeutic agent delivery including: inserting a distal expandable portion of the catheter into the bladder via a urethra, supplying fluid into the bladder through at least one fluid port in the catheter, emitting ultrasound energy and forming cavitations in the gassed fluid, draining the bladder content, and supplying therapeutic fluid into the bladder through at least one therapeutic fluid port in the catheter.
- said fluid is gassed.
- the method includes expanding a distal expandable portion of the catheter prior to supplying therapeutic fluid into the bladder. In some embodiments, the method includes draining and flushing the bladder with saline prior to supplying the gassed fluid into the bladder.
- the method includes stopping emitting ultrasound energy during the draining of the bladder content and/or the supplying of the therapeutic fluid into the bladder through at least one therapeutic fluid port in the catheter. In some embodiments, the method includes further advancing a proximal expandable portion prior to emitting ultrasound energy. In some embodiments, the method includes expanding proximal expandable portion prior to emitting ultrasound energy.
- FIGS. 1 A and 1 B are a plan view and perspective enlarged view of the encircled area of FIG. 1 A , simplified illustrations of a catheter for ultrasonic-driven bladder therapeutic agent delivery in accordance with some embodiments of the invention;
- FIG. 2 is a perspective view simplified illustration of a catheter for ultrasonic-driven bladder therapeutic agent delivery in accordance with some embodiments of the invention
- FIG. 3 is a perspective view simplified illustration of a catheter for ultrasonic-driven bladder therapeutic agent delivery in accordance with some embodiments of the invention
- FIGS. 4 A- 4 D are plan view simplified illustrations of a method of implementation of a catheter for ultrasonic-driven treatment of a bladder, in accordance with some embodiments of the invention.
- FIG. 5 a flow chart of a method for deploying of a catheter for ultrasonic-driven treatment of a bladder wall, in accordance to some embodiments of the invention
- FIGS. 6 A- 6 E are plan view simplified illustrations of a method of implementation of a catheter for ultrasonic-driven treatment of a bladder, in accordance with some embodiments of the invention.
- FIG. 7 is a flow chart of a method for deploying of a catheter for ultrasonic-driven treatment of a bladder wall, in accordance to some embodiments of the invention.
- FIGS. 8 A and 8 B are a plan view and a perspective enlarged view of encircled area in FIG. 8 A , simplified illustration of a catheter for ultrasonic-driven bladder therapeutic agent delivery in accordance with some embodiments of the invention
- FIG. 9 is a side view simplified illustration of a catheter for ultrasonic-driven bladder therapeutic agent delivery in accordance with some embodiments of the invention.
- FIG. 10 is a side view simplified illustration of a catheter for ultrasonic-driven bladder therapeutic agent delivery in accordance with some embodiments of the invention.
- FIG. 11 is a side view simplified illustration of a catheter for ultrasonic-driven bladder therapeutic agent delivery in accordance with some embodiments of the invention.
- FIG. 12 is a side view simplified illustration of a catheter for ultrasonic-driven bladder therapeutic agent delivery in accordance with some embodiments of the invention.
- FIG. 13 is a side view simplified illustration of a catheter for ultrasonic-driven bladder therapeutic agent delivery in accordance with some embodiments of the invention.
- FIG. 14 is a side view simplified illustration of a catheter for ultrasonic-driven bladder therapeutic agent delivery in accordance with some embodiments of the invention.
- FIG. 15 is an exemplary chart of parameters of implementation of a catheter for ultrasonic-driven treatment of a bladder, in accordance with some embodiments of the invention.
- FIG. 16 is a graph of the contractility of the detrusor muscle after each treatment: treatments using catheter for ultrasonic-driven treatment of a bladder compared to untreated tissue, and gold standard 100 units Botox® intravesical injections; and
- FIG. 17 which is a table of efficacy data from two human patients comparing pre-procedure bladder function to 14 days post procedure bladder function.
- cavitation may need to form in a fluid in proximity to the tissue surface to be treated to enhance therapeutic agent delivery.
- the cavitation bubbles need to be prevented from forming near or on the ultrasonic transducer surface, thereby blocking the ultrasonic waves.
- the catheter for ultrasonic-driven bladder therapeutic agent delivery.
- the catheter comprises a tube, one or more transducers mounted on the tube, at least one expandable portion, and a transducer sleeve.
- the transducer sleeve is configured to enclose one or more transducers, wherein a volume is defined between the enclosed transducer and walls of the transducer sleeve.
- the transducer sleeve is disposed between at least two expandable portions.
- the transducer sleeve interconnects at least two expandable portions.
- the tube comprises at least one fluid port configured to supply fluid to or remove fluid from at least one of the at least one expandable portion.
- the expandable portion is inflated by fluid supplied into the portions via the fluid ports.
- the transducer sleeve is expandable.
- the tube comprises at least one therapeutic fluid port configured to supply therapeutic fluid into the bladder.
- the tube comprises at least one therapeutic fluid port at a distal end of the tube.
- the tube comprises at least one therapeutic fluid port between the transducer sleeve and either one of the expandable portions.
- the tube comprises at least one therapeutic fluid port between the transducer sleeve and a proximal expandable portion.
- Proximal means close to the operator and away from the subject being treated and the term “Distal” means distant from the operator and towards the subject being treated.
- fluid can be removed via the therapeutic fluid port.
- the at least one expandable portion at an expanded state is shaped as a sphere or a spheroid. In some embodiments, the at least one expandable portion at an expanded state is toroidal. In some embodiments, the at least one expandable portion at an expanded state comprises a C-shaped cross-section. In some embodiments, the at least one expandable portion at an expanded state comprises an umbrella configuration. In some embodiments, the catheter comprises a expandable portion shaped at an expanded state as a “dog-bone” having two expanded portions interconnected by a transducer sleeve.
- the at least one expandable portion is configured to maintain at least a portion of the internal bladder surface distant from the transducer sleeve.
- the transducer sleeve defines a lumen and the catheter transverses via the lumen.
- one or more transducers are mounted on a portion of catheter inside the transducer sleeve lumen.
- the transducer is surrounded by a fluid that occupies a volume defined between the transducer and the transducer sleeve surrounding the transducer.
- the fluid cools the enclosed transducers.
- the fluid is an acoustic fluid for an efficient delivery of acoustic waves produced by a transducer.
- the transducer sleeve at an expanded state is cylindrical.
- the maximal cross-sectional area of the transducer sleeve at an expanded state is smaller than the maximal cross-sectional area of any one of the expandable portions at an expanded state at any point along their longitudinal axis.
- the maximal cross-sectional area of the transducer sleeve at an expanded state is two thirds of a maximal cross-sectional area of the expandable portions at an expanded state at any point along their longitudinal axis.
- the maximal cross-sectional area of the transducer sleeve at an expanded state is one third of the maximal cross-sectional area of the expandable portions at an expanded state at any point along their longitudinal axis.
- the tube, at least one of the expandable portions, and the transducer sleeve are concentric.
- the expandable portions are configured to occupy a portion of the bladder volume at an inflated state, while defining a treatment volume defined by the transducer sleeve wall, walls of the expanded portions disposed at each end of the transducer sleeve and the bladder wall.
- the expandable portions occupy at least one half of the bladder volume at an inflated state. In some embodiments, the expandable portions occupy between one third and two thirds of the bladder volume when bladder is at an inflated state.
- This configuration directs a therapeutic agent containing fluid within the bladder into the treatment volume in the vicinity of the transducer, while protecting sensitive regions of the bladder e.g., the vesical trigone, at the internal surface of the bladder from being treated by the therapeutic agent and/or being affected by energy transmitted by the transducer.
- at least some of the expandable portions are configured to apply pressure on internal surfaces of the bladder at an expanded state.
- At least one of the expandable portions is configured to engage the bladder wall at an expanded state and block drainage of fluid from the treatment volume to between the expandable portions and the bladder wall.
- an expandable portion at an expanded state maintains the tube concentric with the bladder wall.
- the expandable portions and the transducer sleeve are portions of the same balloon mounted on the tube.
- the transducer sleeve is inelastic having fixed expanded dimensions.
- the transducer sleeve is rigid or comprises a stiffening element.
- the catheter comprises a gap between the transducer and the tube.
- the gap is in the range of 0.05 mm to 4 mm.
- the gap is in the range of 0.1 mm to 2.5 mm.
- the transducer is connected to the tube via spacers.
- a catheter for ultrasonic-driven bladder therapeutic agent delivery comprises a tube, a proximal expandable portion, one or more transducers mounted on the tube between the proximal expandable portion and a distal end of the tube and a transducer sleeve enclosing one or more of the transducers.
- the transducer sleeve has deflated state and an expanded state.
- the proximal expandable portion and the transducer sleeve comprise distinct balloons. In some embodiments, the proximal expandable portion and the transducer sleeve comprise portions of one balloon. In some embodiments the proximal expandable portion at an expanded state is shaped as a sphere or spheroid. In some embodiments the proximal expandable portion at an expanded state is shaped as a toroid. In some embodiments, at least one of the proximal expandable portions at an expanded state comprises a C-shaped cross-section. In some embodiments, at least the proximal expandable portions at an expanded state comprises an umbrella configuration.
- the tube comprises at least one therapeutic fluid port configured to supply therapeutic fluid into the bladder.
- the therapeutic fluid port is located between the transducer sleeve and the proximal expandable portion.
- fluid can be removed via the therapeutic fluid port.
- the proximal expandable portion comprises a balloon that at an expanded state holds the tube at a pre-defined position within the bladder.
- the proximal expandable portion is configured to engage the bladder wall at an expanded state and block a drainage of fluid from a treatment volume within the bladder to between the proximal expandable portion wall and the bladder wall.
- the transducer sleeve at an expanded state is cylindrical having a uniform cross section at least at a portion of its length.
- the maximal cross-sectional area of the transducer sleeve at an expanded state is smaller than the maximal cross-sectional area of the proximal expandable portion at an expanded state at any point along their longitudinal axis.
- the maximal cross-sectional area of the transducer sleeve at an expanded state is two thirds of a maximal cross-sectional area of the proximal expandable portion at an expanded state at any point along their longitudinal axis.
- the maximal cross-sectional area of the transducer sleeve at an expanded state is less than 50% the maximal cross-sectional area of the proximal expandable portion at an expanded state at any point along their longitudinal axis.
- the tube, the proximal expandable portion, and the transducer sleeve are concentric.
- the transducer sleeve at an expanded state does not intersect with an imaginary cone extending between an apex located at the distal end of the tube, and a plane defined by the circumference of the expandable portion at an expanded state.
- the transducer sleeve is inelastic having limited expanded dimensions.
- the transducer sleeve is rigid or comprises a stiffening element.
- the therapeutic agent fluid may be a non-gassed fluid.
- the amount of cavitation bubbles generated in the therapeutic agent fluid are increased by providing a gassed therapeutic agent fluid. Therefore, according to an aspect of some embodiments of the present invention there is provided a method for increasing the amount of cavitation bubbles within a therapeutic agent used with a catheter for ultrasonic-driven bladder therapeutic agent delivery.
- the method comprises pressurizing a sterile liquid with a gas and generating a “gassed liquid”.
- the method comprises releasing a therapeutic agent into the gassed liquid and forming a gassed therapeutic fluid.
- the method comprises inserting the gassed therapeutic fluid into the bladder via a catheter for ultrasonic-driven bladder therapeutic agent delivery and forming cavitation in the therapeutic fluid.
- the method comprises, for example pressurizing a sterile liquid with a gas comprises pressurizing at a pressure of about 8 to 30 atmospheres and for a predetermined duration.
- the therapeutic agent fluid is mixed with a non-gassed fluid instead of a gassed fluid.
- the catheter comprises an expandable portion such as a balloon, a stent, or any combination thereof.
- at least one expandable portion comprises a stent.
- FIG. 1 is a side view with a perspective enlarged view, simplified illustration of a catheter for ultrasonic-driven bladder therapeutic agent delivery in accordance with some embodiments of the invention.
- a catheter 10 comprises a tube 11 , a transducer 30 mounted on tube 11 and an expandable portion 20 mounted on tube 11 and enclosing transducer 30 .
- the expandable portion 20 is a balloon.
- expandable portion 20 comprises two expandable portions 24 and 26 coupled to and sandwiching a transducer sleeve 22 disposed in between.
- the tube 11 comprises at least one fluid ports 14 and 15 , configured to supply or to remove fluid out of at least one of the balloon 20 portions 22 , 24 and 26 .
- the transducer sleeve 22 encapsulates the transducer 30 and defines a volume between the walls of the transducer sleeve 22 and the transducer.
- the tube comprises one or more conduits, or in other words, fluid supply channels, (not shown) supplying fluid from a fluid source to one or more ports.
- fluid supply channels are interchangeable.
- the one or more fluid supply channels are disposed inside the tube or along an outer surface of the tube.
- a fluid flow is generated within the balloon 20 and at least within the internal volume of the transducer sleeve 22 by providing fluid via one of the fluid ports, e.g. port 14 , and removing fluid via another fluid port, e.g. port 15 .
- the fluid provided into the balloon comprises an acoustic fluid.
- acoustic fluid relates to a fluid with high cavitation energy threshold to prevent formation of cavitation bubbles in this liquid during operation of the ultrasound that would interfere with acoustic waves, and prevent damage to the catheter.
- the acoustic fluid allows efficient progression of ultrasound energy.
- An aspect of this fluid is that it reduces cavitation, which may block ultrasound energy from progressing from the transducer to the bladder internal surface.
- Such fluid may be a degassed fluid, e.g. a degassed solution such as saline which went through boiling, or a solution which its gas content was filtered out.
- the acoustic fluid assists in transmitting the acoustic waves produced by the transducer 30 through the surface of the transducer sleeve 22 to the therapeutic fluid surrounding the transducer sleeve.
- the acoustic fluid can also cool the enclosed transducers 30 , for example by heat convection. By the cooling of the transducers, the transducers can be operated in desired parameters for a longer treatment duration. In addition, the overheating of the bladder tissues by heated transducers is avoided.
- the acoustic fluid provided into the transducer sleeve 22 does not contain gas bubbles to serve as nucleation seeds for the generation of cavitation and therefore distances the cavitation phenomenon from the transducer 30 and towards the bladder wall.
- the ultrasound waves travel from the transducer through the acoustic fluid without generating cavitation, hence are free to travel through this medium towards the surface of the sleeve 22 .
- the waves travel through the therapeutic fluid located in a therapeutic volume between the sleeve and the bladder towards the bladder tissue.
- cavitation is generated, thereby, resulting in the delivery of the therapeutic agent into the bladder. This allows the transducer to be disposed farther from the bladder internal surface than transducers exposed to therapeutic fluid inside the bladder. Production of cavitation increases the efficacy of the ultrasound treatment as described in detail in U.S. patent application Ser. No. 15/561,733 to the same inventors.
- the tube 11 comprises a tip 16 which comprises a plurality of fluid port(s) 17 .
- tip 16 is convex and configured to allow easier insertion of the catheter into the bladder and reduce accidental damage to the interior surface of the bladder during the deployment of the catheter within the bladder.
- tip 16 has oblong geometry having fluid ports at a distal end of the tip. In some embodiments, tip 16 has no ports.
- the bladder fluid ports 17 can be used, for example, for one or more of the following functions: inserting therapeutic fluid into the bladder, removing therapeutic fluid out of the bladder, inserting tissue cleaning fluid, such as saline to remove a therapeutic fluid, and removing fluid out of the bladder, e.g. urine filling a urine bladder prior to treatment.
- the shape of tip 16 is one of a toroid, torus, disk, sphere, and semi-sphere.
- the tip 16 is rigid or semi-rigid.
- the port(s) 17 are distributed along at least a portion of the circumference of the tip 16 .
- the tip 16 comprises a surface 40 positioned distally in relation to the port(s) 17 .
- the surface 40 is rounded.
- the tip 16 is blind. In some embodiments, fluid flowing within tube 11 exits port(s) 17 .
- a potential advantage of a plurality of openings is in that multiple ports provide a redundancy in cases of clogged ports when inserting or removing fluid.
- at least one therapeutic fluid port can be disposed at the tube, between the transducer sleeve and the expandable portion.
- at least one therapeutic fluid port can be disposed at the tube at a proximal tube portion which is not covered by any expandable portion.
- the fluid port(s) 17 are positioned radially around the longitudinal axis of the catheter and/or tube. In some embodiments, the fluid port(s) 17 are positioned such that a fluid streaming from the fluid port(s) 17 is ejected at a nonzero angle in relation to the longitudinal axis of the catheter and/or tube.
- the catheter 10 when the catheter 10 is inserted into a bladder such that tip 16 is urged against the wall of the bladder (e.g., the surface opposite the trigone) marked region 5 ′′, or other portions of the urinary bladder wall, the bladder wall does not obstruct the fluid port(s) 17 .
- the tip 16 comprises a distal opening of the distal portion 11 b of tube 11 . In some embodiments, the tip 16 comprises at least one port 17 at the surface 40 . In some embodiments, the tip 16 comprises a cover comprising at least one aperture, such as a mesh. In some embodiments, the tip 16 cover is rigid or semi rigid. In some embodiments, the cover defines a volume around the tip 16 .
- the catheter 10 when the catheter 10 is inserted into a bladder such that the cover of tip 16 is urged against the wall of the bladder, for example, the distal portion of the bladder (such as the surface opposite the trigone) marked region 5 ′′, or other portions of the urinary bladder wall, the bladder wall does not obstruct at least one aperture of the tip 16 cover.
- At least one of the transducer, at least one of the expandable portion, and the tube are concentric. In some embodiments, at least two expandable portions are concentric. In some embodiments, the transducer and at least one expandable portion are concentric. In some embodiments, the transducer sleeve and at least one expandable portion are concentric. In some embodiments, the transducer sleeve and the transducer are concentric.
- An advantage of the concentric positions of the catheter, expandable portion, transducer sleeve and/or transducer is in that the catheter maintains equal distance between the internal bladder wall and the transducer, such that the treated portion of the bladder wall may receive equal or nearly-equal treatments. Additionally, in some embodiments, the treated portion of the bladder wall may receive predetermined varying treatment.
- the tube 11 comprises one or more conduits which supply fluid to one or more of the ports 14 / 15 / 17 .
- each conduit opens to a specific port 14 / 15 / 17 .
- each conduit opens to a separate port 14 / 15 / 17 .
- a conduit opens to at least one of the ports 14 / 15 / 17 .
- tube lumen 11 comprises at least one conduit. In some embodiments, at least one conduit is in fluid communication with a proximal opening 34 / 36 / 38 of the catheter 10 .
- the catheter 10 comprises at least one proximal opening 34 / 36 / 38 through which fluid passes into and/or out of one or more ports 14 / 15 / 17 .
- a proximal opening 34 / 36 / 38 is in fluid communication with a reservoir for fluid, such as, for example, a therapeutic fluid, a fluid (e.g. saline), a gassed fluid, and an acoustic fluid.
- a proximal opening 34 / 36 / 38 is in fluid communication with a drainage bag.
- at least one conduit is coupled to one or more of the proximal openings 34 / 36 / 38 .
- each of the proximal openings 34 / 36 / 38 is in fluid communication with at least one of the ports 14 / 15 / 17 .
- FIG. 2 is a perspective view simplified illustration of implementation of an ultrasonic-driven bladder therapeutic agent delivery inside a bladder 1 in accordance with some embodiments of the invention.
- expandable portions 24 and 26 are spheroid in geometry and in an expanded state.
- both expandable spheroid portions 24 and 26 occupy a portion of the bladder volume, thereby forming a treatment volume 7 surrounding the transducer sleeve 22 between the expandable spheroid portions 24 and 26 and the bladder wall 5 .
- a potential advantage of this configuration is in that a therapeutic agent disposed within the bladder 1 will be directed into the treatment volume 7 between the transducer 30 and the bladder wall 5 , limiting the treatment on bladder tissues to section 5 ′ of the bladder wall and the treatment volume 7 and benefiting from the full effect of cavitation formed by transducer 30 . Additionally, in some embodiments, this configuration directs a therapeutic agent containing fluid within the bladder 1 into the treatment volume 7 , while protecting regions e.g., the vesical trigone, at the internal surface of the bladder 1 from being treated by the therapeutic agent and/or energy transmitted by the transducer 30 . In some embodiments, the expandable portions 24 and 26 occupy between 30% and 70% of the bladder volume at an expanded state. In some embodiments, the expandable portions 24 and 26 occupy between 40% and 60% of the bladder volume at an expanded state.
- a bladder wall is undulated in shape.
- the inflated balloon 20 applies tension in the internal surface 5 of the bladder 1 in a plurality of directions, thereby straightening at least a portion of the bladder wall of the bladder at least in region 5 ′ bordering the treatment volume 7 between expandable portion 24 and 26 as shown in FIG. 2 .
- Expandable portions 24 and 26 can be designed to have a circumference at a fully expanded state that will define a pre-determined distance L 1 between the transducer 30 and the bladder treated surface 5 ′.
- a uniform treatment is achieved by having the treated tissues at equidistance from the transducer.
- the concentration of the therapeutic agent within the therapeutic fluid are determined by the predictable treatment volume 7 . Straightening and stretching the bladders' tissues contribute to the efficacy of the treatment by increasing the permeability of the therapeutic agent into the bladder tissues.
- such structural configuration stabilizes the bladder wall and increases the safety of the procedure by preventing the collapse of the bladder wall onto or close to the hot transducer surface.
- the transducer sleeve 22 prevent a direct contact between the bladder and the transducer 30 .
- one or more of the expandable portions is a stent.
- the procedure is carried out when the bladder is positioned vertically or close to vertically wherein the trigone is lowest portion of the urinary bladder.
- the distal expandable portion 26 does not seal a distal portion of the bladder (e.g., the surface opposite the trigone) marked region 5 ′′.
- the therapeutic fluid provided through ports 17 can then flow into the volume 7 , e.g. by gravity or by pressure gradient.
- the proximal expandable portion 24 engages the proximal surface of the bladder.
- the expandable portion 24 can block a drainage of fluid from the therapeutic volume 7 being pressed against the bladder wall.
- the expandable portion 24 can be pressed against and seal the proximal surface of the bladder (e.g. by static forces, such as gravity, fluid pressure, distal spheroid pressing against a distal bladder surface).
- static forces such as gravity, fluid pressure, distal spheroid pressing against a distal bladder surface.
- the proximal and/or distal expandable portion 24 / 26 shields portions of the bladder wall from ultrasonic energy. In some embodiments, the proximal expandable portion 24 shields the trigone from ultrasonic energy. In some embodiments, the proximal and/or distal expandable portion 24 / 26 acts as a vessel for a cooling fluid flow which increases heat dissipation from the transducer.
- At least one of the proximal and/or distal expandable portion 24 / 26 is filled with fluid which has high acoustic impedance and therefore is non-conducive to ultrasound energy.
- the non-conducive fluid inflates at least one of the proximal and/or distal expandable portion 24 / 26 .
- the non-conducive fluid prevents transmission of ultrasound energy to the untreated areas of the bladder (e.g., the trigone).
- a potential advantage of having the non-conducive fluid within one or more expandable portions 24 / 26 is in that ultrasound energy is not transmitted to portions of the bladder which are not treated.
- expandable portion 24 serves as a catheter support and fixes the position of the tube 11 within the bladder 1 .
- fluid within one or more expanded portions engaging an internal surface 5 of the bladder 1 cools the bladder by heat transfer between the bladder wall and the fluid.
- the volume and/or shape of the expandable portions 24 / 26 determine the distance between the bladder treated surface 5 ′ and the transducer 30 . In some embodiments, the volume and/or shape of the expandable portions 24 / 26 determine the distance between the bladder treated surface 5 ′ and the transducer sleeve 22 . In some embodiments, the distance between the bladder treated surface 5 ′ and the transducer 30 and/or the transducer sleeve 22 is predetermined.
- the temperature of the bladder treated surface 5 ′ is correlated with the heat given off by the transducer. Therefore, increasing the distance between the transducer 30 and the bladder treated surface 5 ′ prevents over-heating of the bladder treated surface 5 ′. In some embodiments, increasing the distance between the transducer 30 and the bladder treated surface 5 ′ permits heating of the transducer 30 to higher temperatures, for example, by increasing on-time and/or frequency emitted by the transducer.
- increasing the frequency emitted by the transducer increases the efficacy of the treatment by increasing the cavitation within the therapeutic fluid (and/or combination of the gassed fluid and therapeutic fluid). In some embodiments, increasing the on-time of the transducer increases the efficacy of the treatment by increasing the cavitation within the therapeutic fluid (and/or combination of the gassed fluid and therapeutic fluid).
- expandable portions 24 and 26 define a cylinder 23 therebetween, the wall of the cylinder outlined by broken lines, congruent with the largest circumference of the expandable portions 24 / 26 at Y 1 and Y 2 respectively.
- the maximal cross-sectional area of the transducer sleeve 22 taken at Y 3 is smaller than the maximal cross-sectional area of the expanded portions 24 and 26 .
- a diameter D 10 of expandable portions 24 and 26 is between 20 mm and 40 mm at an expanded state. In some embodiments, a diameter D 10 of expandable portions 24 and 26 is between 20 and 40 mm at an expanded state.
- a diameter D 20 of a transducer sleeve 22 is between 5 mm and 15 mm. In some embodiments, a diameter D 20 of a transducer sleeve 22 is between 6 mm and 12 mm. In some embodiments, a diameter D 20 of a transducer sleeve 22 is between 8 mm and 10 mm. In some embodiments a length L 30 of the transducer sleeve is between 5 and 25 mm at an expanded state. In some embodiments a length L 30 of the transducer sleeve is between 10 and 15 mm at an expanded state.
- the transducer sleeve at an expanded state is cylindrical having a uniform cross section at least at a portion of its length.
- the maximal cross-sectional area of the transducer sleeve at an expanded state is smaller than the maximal cross-sectional area of the proximal expandable portion at an expanded state at any point along their longitudinal axis.
- the maximal cross-sectional area of the transducer sleeve at an expanded state is two thirds of a maximal cross-sectional area of the proximal expandable portion at an expanded state at any point along their longitudinal axis.
- the maximal cross-sectional area of the transducer sleeve at an expanded state is less than 50% the maximal cross-sectional area of the proximal expandable portion at an expanded state at any point along their longitudinal axis.
- the tube, the proximal expandable portion, and the transducer sleeve are concentric.
- the length of the transducer 30 is 3-20 mm. In some embodiments, the length of the transducer 30 is 4-14 mm. In some embodiments, the length of the transducer 30 is 5-10 mm. In some embodiments, the length of the transducer 30 is 6 mm.
- the width of the transducer 30 is 3-14 mm. In some embodiments, the width of the transducer 30 is 3-7 mm. In some embodiments, the width of the transducer 30 is 3-5 mm. In some embodiments, the width of the transducer is 4 mm.
- the thickness of the transducer 30 is 10-40 mm. In some embodiments, the thickness of the transducer 30 is 15-30 mm. In some embodiments, the thickness of the transducer 30 is 15-23 mm. In some embodiments, the thickness of the transducer 30 is 20 mm.
- the balloon wall comprises regions having variable elasticity so that, for example, only portions of the balloon wall are elastically expandable.
- diametrically opposed faces 24 a and 24 c ( FIG. 1 ) of expandable portion 24 can be produced as an inelastic face, while a face 24 b along the circumference of expandable portion 24 is elastically flexible, hence the expansion of portion 24 will be greater radially expansion along catheter tube 11 .
- At least one of the expandable portions at an expanded state is shaped as at least one of a sphere, a spheroid and a toroid. In some embodiments, at least one of the expandable portions at an expanded state comprises a C-shaped cross-section. In some embodiments, at least one of the expandable portions at an expanded state comprises an umbrella configuration.
- the transducer sleeve at an expanded state is cylindrical. In some embodiments, the maximal cross-sectional area of the transducer sleeve at an expanded state is smaller than the maximal cross-sectional area of any one of the expandable portions at an expanded state at any point along their longitudinal axis. In some embodiments, the maximal cross-sectional area of the transducer sleeve at an expanded state is two thirds of a maximal cross-sectional area of the expandable portions at an expanded state at any point along their longitudinal axis.
- the maximal cross-sectional area of the transducer sleeve at an expanded state is one third of the maximal cross-sectional area of the expandable portions at an expanded state at any point along their longitudinal axis.
- the tube, at least one of the expandable portions, and the transducer sleeve are concentric.
- the expandable portions are configured to occupy a portion of the bladder volume at an inflated state, while defining a treatment volume defined by the transducer sleeve wall, walls of the expanded portions disposed at each end of the transducer sleeve and the bladder wall.
- the expandable portions occupy at least one half of the bladder volume at an inflated state. In some embodiments, the expandable portions occupy between one third and two thirds of the bladder volume when bladder is at an inflated state.
- This configuration directs a therapeutic agent containing fluid within the bladder into the treatment volume in the vicinity of the transducer, while protecting sensitive regions of the bladder e.g., the vesical trigone, at the internal surface of the bladder from being treated by the therapeutic agent and/or being affected by energy transmitted by the transducer.
- at least some of the expandable portions are configured to apply pressure on internal surfaces of the bladder at an expanded state.
- shaping of any of the balloons can done by: molding, differential thickness, varying materials, integral elements, etc.
- Another method for shaping any of the balloon portions can be by limiting its expansion by external elements, such as a sleeve or a net.
- the tube 11 has a uniform cross section throughout its length.
- a distal portion 11 b of tube 11 comprises a smaller diameter than the diameter of proximal portion 11 a of tube 11 .
- portion 11 b comprises the distal tip 16 .
- portion 11 b is connected to tube 11 under a proximal edge of transducer 30 .
- transducer 30 is mounted on portion 11 b of tube 11 so that an external surface of transducer 30 is positioned flush with proximal portion 11 a of tube 11 .
- portion 11 b comprises a narrow tube portion inserted within tube 11 .
- each of ports 14 / 15 are supplied by distinct fluid supply channel so that supplying fluid to expandable portion 26 via port 15 does not necessarily expand expandable portion 24 and vice versa, even though expandable portions 24 / 26 are in fluid communication via transducer sleeve 22 .
- port 15 is associated with a distinct fluid supply channel of the tube 11 .
- port 14 is configured to be closed when providing fluid by port 15 .
- a potential advantage in the configuration of ports 14 / 15 is in that during deployment, expandable portion 26 is configured to be inflated while expandable portion 24 is still within urethra 3 , i.e., without expanding expandable portion within urethra 3 , which may be painful to the subject being treated.
- FIGS. 4 A to 4 D are plan view simplified illustrations of the method of implementation of a catheter for ultrasonic-driven treatment of a bladder. As shown in FIGS. 4 a to 4 d , the catheter for ultrasonic-driven treatment of a bladder is deployed by:
- FIG. 5 is a flow chart of a method for deploying of a catheter for ultrasonic-driven treatment of a bladder wall in accordance to some embodiments of the invention and to corresponding FIGS. 6 A to 6 E , which are side-view simplified illustrations of the method of implementation of a catheter for ultrasonic-driven treatment of a bladder.
- the catheter 10 for ultrasonic-driven treatment of a bladder 1 is deployed by:
- the method comprises expanding the proximal expandable portion and trapping the therapeutic fluid between the distal expandable portion and the proximal expandable portion.
- a potential advantage in using the method for deployment of the ultrasonic-driven catheter 10 is in that most of the therapeutic fluid does not remain trapped at a distal volume between the distal expandable portion 26 and the bladder wall 5 ′′ opposite to the bladder trigone.
- FIG. 6 A is a plan view simplified illustration of the insertion of distal expandable portion 26 into bladder 1 through urethra 3 .
- the proximal expandable portion 24 remains within the urethra 3 .
- FIG. 6 B is a plan view simplified illustration of the expanding of distal expandable portion 26 to an expanded state by providing fluid into distal expandable portion 26 via fluid port 15 (for example, as depicted by arrow 600 ).
- the distal expandable portion 26 and the proximal expandable portion 24 are in fluid communication.
- the fluid remains in distal expandable portion 26 , flow in the direction of proximal expandable portion 24 countered by external pressure applied to proximal expandable portion 24 by the urethra wall.
- the proximal expandable portion 24 remains contracted within the urethra due to pressure applied to the proximal expandable portion 24 by the urethra walls.
- the proximal expandable portion 24 remains mostly contracted within the urethra.
- FIG. 6 C is a plan view simplified illustration of supplying of therapeutic fluid through the therapeutic fluid port(s) 17 .
- the method comprises supplying therapeutic fluid through the therapeutic port(s) 17 into the volume 46 defined by the distal expanding portion 26 and the bladder wall (for example, as depicted by arrow 602 ).
- FIG. 6 D is a plan view simplified illustration of the further advancing proximal portion 24 into bladder 1 through urethra 3 .
- proximal portion 24 is freed from external pressure applied thereto by the urethra walls and at least a portion of the fluid inside the distal expandable portion 26 flows into the proximal expandable portion 24 to equalize pressures within expandable portions 24 and 26 in accordance with the law of LaPlace.
- fluid inside the distal expandable portion 26 flows into the portion of the proximal expandable portion 24 which is within the bladder 1 .
- the volume of the distal expandable portion 26 decreases due to fluid flow into the proximal expandable portion 24 . In some embodiments, the decrease in volume of the distal expandable portion 26 increases flow of therapeutic fluid into the bladder volume 48 surrounding the transducer sleeve 22 . In some embodiments, the decrease in volume of the distal expandable portion 26 creates or increases a distance 50 between the distal expandable portion 26 and the bladder wall, which increases flow of therapeutic fluid to volume 48 . In some embodiments, the partially expanded proximal expandable portion 24 provides a barrier for therapeutic fluid flowing into volume 48 .
- FIG. 6 E is a plan view simplified illustration of the expanding of portion 24 to an expanded state by providing fluid into portion 24 via fluid port 14 (for example, as depicted by arrow 604 ).
- expanding proximal expandable portion 24 to an expanded state by providing fluid via port 14 increases the volumes of both the proximal and distal expandable portions 24 / 26 .
- the expandable portions 24 / 26 are separate balloons. In some embodiments, during or after the further advancement of the proximal portion 24 into bladder 1 , at least a portion of the fluid inside the distal expandable portion 26 is removed via fluid port 15 . In some embodiments, the volume of the distal expandable portion 26 decreases. In some embodiments, during or after the further advancement of the proximal portion 24 into bladder 1 , the proximal expandable portion 26 is at least partially expanded by providing fluid via fluid port 14 . In some embodiments, once therapeutic fluid enters the volume 48 surrounding the transducer sleeve 22 , the distal expandable portion 26 is expanded by providing fluid into the distal expandable portion 26 via fluid port 15 .
- the ultrasonic-driven treatment performed by catheter 10 inserted within a bladder 1 is carried out by a method in accordance with some embodiments of the invention and includes:
- the ultrasonic-driven treatment performed by catheter 10 inserted within a bladder 1 is terminated by the following method, according to some embodiments of the invention:
- FIG. 7 is a flow chart of a method for the deployment of a catheter for ultrasonic-driven treatment of a bladder wall and the treatment of the bladder in accordance to some embodiments of the invention.
- the method for deployment of catheter 10 in bladder 1 is carried out as follows:
- the method comprises expanding the proximal expandable portion and trapping the therapeutic fluid between the distal expandable portion and the proximal expandable portion.
- FIGS. 8 A and 8 B are a side view and perspective view simplified illustration of a catheter for ultrasonic-driven bladder therapeutic agent delivery in accordance with some embodiments of the invention.
- a catheter 110 comprises a tube 111 , a proximal balloon 124 mounted on the tube 111 , and an expandable transducer sleeve 122 .
- a distal portion 111 b of tube 111 comprises a smaller diameter than the diameter of proximal portion 111 a of tube 111 .
- portion 111 b comprises the distal tip 117 .
- portion 111 b is connected to tube 111 under a proximal edge of transducer 130 .
- transducer 130 is mounted on portion 111 b of tube 111 so that an external surface of transducer 130 is positioned flush with proximal portion 111 a of tube 111 .
- portion 111 b comprises a narrow tube portion inserted within tube 111 .
- a transducer 130 is mounted on tube 111 portion 111 b between the proximal expandable portion 124 and a distal end 117 of the tube.
- the transducer sleeve 122 accommodates and encapsulates the transducer 130 and enables a flow of fluid at the internal volume defined by the walls of transducer sleeve 122 .
- the tube 111 comprises one or more therapeutic fluid port(s) 116 at a proximal portion 111 a of the tube 111 , which is free of the expandable portions 122 and 124 and is exposed to the bladder volume.
- proximal balloon 124 is expandable from a collapsed state to an expanded state.
- the expanded state is defined as the maximal inelastic expansion of the balloon.
- the expanded state of the balloon is defined as a maximal elastic expansion wherein the balloon is elastic.
- the tube 111 comprises one or more fluid ports 114 , 115 a and 115 b , configured to supply fluid to or remove fluid from at least one of the expandable portions 122 and 124 . Expandable portions 122 and 124 are expandable by supplying fluid under positive pressure through at least one of the fluid ports 114 , 115 a and 115 b .
- the tube 111 comprises one or more fluid supply channels (not shown), either inside the tube 111 and/or along an outer surface of the tube.
- a fluid flow is generated within a lumen defined by walls of transducer sleeve 122 by providing fluid via one of the fluid ports, e.g. port 115 a , and removing fluid via another fluid port, e.g. port 115 b .
- fluid supply port, e.g. port 115 a and fluid removal port, e.g. port 115 b are disposed on diametrically opposed surfaces of catheter 110 .
- fluid supply port e.g.
- port 115 a is located on tube 111 portion 111 b whereas the fluid removal port, e.g. port 115 b is disposed on tube 111 .
- fluid supply port, e.g. port 115 a and fluid removal port, e.g. port 115 b are disposed on opposite sides of transducer 130 .
- fluid supply port, e.g. port 115 a , and fluid removal port, e.g. port 115 b are circumferentially rotated in respect to each other.
- the fluid inputted into the balloon comprises an acoustic fluid.
- the acoustic fluid maintains a fixed distance between the surface of transducer 130 and transducer sleeve 122 .
- the acoustic fluid assists in cooling the enclosed transducers 130 , for example by heat convection.
- cooling of the transducers helps in their operating in desired parameters for a longer treatment duration, thus, avoiding overheating the tissues while providing an effective treatment.
- removing heat from the transducers prevents overheating of the bladder tissue, which permits an increase in the range of the operational parameters, such as, for example, longer treatment time and/or an increase in transducer frequency.
- the procedure is carried out when the bladder is positioned vertically or close to vertically wherein the trigone is lowest portion of the urinary bladder.
- FIG. 9 which is a side view simplified illustration of implementation of an ultrasonic-driven bladder therapeutic agent delivery inside a bladder in accordance with some embodiments of the invention
- the proximal balloon 124 at an expanded state, engages the proximal surface of the bladder at the trigone area.
- the proximal balloon 124 occupies a volume of the bladder 100 , thereby forming a treatment volume 107 .
- Balloon 124 at an expanded state blocks drainage of fluid from volume 107 via the balloon wall which is urged against the bladder wall 105 .
- balloon 124 is urged against and seals the proximal surface (trigone area) of the bladder 105 ′, for example by static forces, such as gravity or fluid pressure.
- the therapeutic fluid remains within volume 107 during the treatment, while the proximal surface (trigone area) of the bladder 105 ′ located distally to proximal balloon 124 remains protected from exposure to the therapeutic fluid and the acoustic energy.
- balloon 124 serves as a catheter base and fixes the position and orientation of the tube 111 in respect to the bladder as well as the elements mounted on the tube within the bladder 100 .
- therapeutic fluid can be provided into the bladder in an amount which will fill only a portion of the bladder.
- the level of fluid will be lower than pre-determined surfaces, so will not be treated by the therapeutic fluid and acoustic energy.
- FIG. 10 which is a side view simplified illustration of implementation of an ultrasonic-driven bladder therapeutic agent delivery inside a bladder in accordance with some embodiments of the invention, therapeutic fluid partially fills volume 107 of the bladder 100 . Since the bladder 100 is oriented vertically, the direction of gravitation indicated by an arrow (G), the therapeutic fluid remains in between levels E 1 and E 2 . During the treatment, only a portion of the bladder wall which is located distally (above) to proximal balloon 124 in region 105 ′′ and within volume 107 will receive the therapeutic fluid and acoustic energy.
- the regions of the bladder wall affected by the treatment are defined by the following dimensions of elements of the catheter 100 such as, for example: the cross section of the proximal balloon 124 , the distance between port 116 and face 124 b , and the distance between port 116 and the transducer sleeve 122 .
- the transducer sleeve 122 isolates the transducer 130 from the therapeutic agent and prevents cavitation bubbles from forming near or on the transducer surface. Thereby, the transducer can be disposed farther from the bladder internal wall than in the absence of a transducer sleeve 122 . This allows distribution of cavitation bubbles within treatment volume 107 , to invoke cavitation on the bladder wall, thus increasing the efficacy of energy emitted towards the bladder wall by the transducers.
- Some parameters that determine the expanded geometrical shape of the transducer sleeve 122 can be: size and number of the transducers 130 it encloses, flow characteristic of the fluid within its internal volume, desired volume of the bladder extraneous to the transducer sleeve, etc.
- the transducer sleeve 122 can be characterized to be inelastic having a fixed expanded length, to be rigid or to comprise a stiffening element, and in some embodiments the sleeve can be pressurized to higher pressure than other expandable portions.
- FIG. 11 is a side view simplified illustration of a catheter for ultrasonic-driven bladder therapeutic agent delivery in accordance with some embodiments of the invention.
- the geometry of the catheter 150 protects the wall of the bladder from collapsing onto transducer sleeve 122 .
- a bladder wall tends to conform to the geometry of the catheter 10 forming a cone 140 depicted in FIG. 11 by a phantom-line triangle 143 .
- tip 117 of catheter 150 forms an apex 141 of cone 140 and a base 142 of cone 140 is formed at the maximal cross-sectional area of the proximal balloon 124 at an inflated state.
- the wall of the bladder is prevented from collapsing onto and contacting transducer sleeve 122 at an inflated state.
- This constraint can be driven for example by a requirement to maintain a distance between the transducer sleeve walls and the enclosed transducer e.g. in case the bladder surface collapses and engages the sleeve 122 , to avoid bending of the sleeve, etc.
- a diameter D 110 of proximal balloon 124 is between 20 mm and 50 mm at an expanded state. In some embodiments, a diameter D 110 of proximal balloon 124 is between 30 mm and 38 mm at an expanded state. In some embodiments, a diameter D 120 of a transducer sleeve 122 is between 5 mm and 20 mm. In some embodiments, a diameter D 120 of a transducer sleeve 122 is between 8 mm and 17 mm. In some embodiments, a diameter D 120 of a transducer sleeve 122 is between 12 mm and 14 mm. In some embodiments a length L 130 of the transducer sleeve is between 5 and 50 mm at an expanded state. In some embodiments a length L 130 of the transducer sleeve is between 15 and 40 mm at an expanded state.
- catheter 150 can comprise two distinct balloons such as shown, for example, in FIGS. 8 to 12 .
- different pressures or different pressuring fluids can be used for the expansion of the proximal balloon 124 and the transducer sleeve 122 portions.
- only portions of the wall of balloon 124 are elastically inflatable, while other portions are inelastic.
- a method for deployment of the ultrasonic-driven catheter according to some embodiments of the invention includes:
- a method for treatment of a bladder wall using an ultrasonic-driven catheter includes:
- the ultrasonic-driven treatment performed by the catheter 110 inserted within a bladder 100 is terminated by the following method, according to some embodiments of the invention:
- the deployment of the catheter for ultrasonic-driven treatment of a bladder wall and treatment is carried out within the bladder, by the following method:
- At least one of the expandable portions at an expanded state is shaped as at least one of a sphere, a spheroid or a toroid. In some embodiments, at least one of the expandable portions at an expanded state comprises a C-shaped cross-section. In some embodiments, at least one of the expandable portions at an expanded state comprises an umbrella configuration.
- FIG. 12 shows an embodiment in which the expandable portion 824 is toroidal in geometry.
- catheter 811 comprises a therapeutic fluid port 816 between a transducer sleeve 822 and the expandable portion 824 .
- toroidal expandable portion 824 when inflated, expands distally, along catheter tube 811 towards tip 802 as indicated by arrows 850 and directing any therapeutic fluid supplied via therapeutic fluid port 816 into treatment volume 807 to surround transducer 830 thus increasing treatment efficacy.
- a potential advantage in this configuration is in that the treatment area is more limited and therefore defined more accurately and that a lower amount of therapeutic fluid is required to treat a given area of bladder wall limiting waste of therapeutic fluid.
- Shaping of any of the balloons can done by: molding, differential thickness, varying materials, integral elements, etc.
- Another method for shaping any of the balloon portions can be by limiting its expansion by external elements, such as a sleeve or a net.
- the catheter for ultrasound-driven treatment of a bladder is configured to comprise energy supply conduits for the ultrasound transducer 30 / 130 / 830 .
- the catheter for ultrasound-driven treatment of a bladder comprises one or more thermocouples disposed within one or more of the expandable portions.
- the thermocouple is configured to measure fluid temperature within the treatment volume.
- one or more thermocouples are configured to measure temperature of the bladder wall tissue to prevent overheating of the wall of the bladder.
- one or more of the thermocouples are coupled to the bladder wall.
- the thermocouple is configured to measure fluid temperature within one or more of the expandable portions and/or the transducer sleeve.
- the thermocouple is configured to measure temperature over the surface of the transducer.
- the catheter for ultrasound-driven treatment of a bladder comprises one or more pressure sensors within at least one of the expandable portions configured to monitor fluid pressure within the expandable portion.
- the transducers 30 / 130 are cylindrical. However, in other embodiments, the transducer can be flat. In some embodiments, transducers 30 / 130 are mounted on the tube 11 / 111 by spacers 32 / 132 and 33 / 133 . Fixation of the transducer at a pre-determined location on the tube provides predictable and repeatable energy parameters.
- the spacers 32 / 132 and 33 / 133 are configured to support the transducers elevated from tube 11 / 111 , so to form a gap between the transducer and the tube 11 / 111 .
- the gap is in the range between 0.05 mm and 4 mm. In some embodiments the gap is in the range between 0.1 mm and 2.5 mm.
- the gap is filled by acoustic fluid flowing within the enclosing transducer sleeve 22 / 122 , which can result in cooling of the transducer. In some embodiments, the gap is filled by acoustic fluid which flows within the transducer sleeve 22 / 122 , thereby transferring heat form the transducer.
- the one or more of the spacers 32 / 33 / 132 / 133 is mounted on the tube 11 / 111 .
- the transducer 30 / 130 is mounted on one or more of the spacers 32 / 33 / 132 / 133 .
- a transducer 30 / 130 is positioned onto one spacer 32 / 33 / 132 / 133 .
- the transducer 30 / 130 is positioned on a plurality of spacers 32 / 33 / 132 / 133 .
- the length of the spacer 32 / 33 / 132 / 133 is larger than the outermost radius of the spacer 32 / 33 / 132 / 133 . In some embodiments, the length of the spacer is at least 50% of the length of the transducer 30 / 130 . In some embodiments, the length of the spacer 32 / 33 / 132 / 133 is up to 30% of the length of the transducer 30 / 130 .
- the spacer 32 / 33 / 132 / 133 adds concentricity, electrical protection, and mechanical scaffold to the catheter for ultrasonic-driven bladder drug delivery.
- distancing the transducer from the catheter and/or tube provides electrical insulation by having an isolation medium (e.g., air) between the transducer and the catheter.
- FIGS. 13 and 14 are simplified illustrations of side views of a catheter for ultrasonic-driven bladder drug delivery, in accordance with some embodiments of the present disclosure.
- normally open stents e.g. expandable stents 224 , 324 , 326
- normally open stents replaces at least some of expandable portions disclosed in the preceding embodiments, such as 24 , 26 , 124
- normally open stents e.g. expandable stents 224 , 324 , 326 .
- Each of the stents 224 , 324 , 326 are configured as normally open and remains enclosed within a stent sleeve (not shown) prior to inserting the catheter 210 / 310 into a bladder.
- the stents are configured to open upon exposing out of the stent sleeve and to engage the bladder wall.
- Any of the stents can have a fluid sealing surface to block fluid within a bladder cavity volume defined within the bladder on one side of the sealing surface to flow into a bladder cavity volume defined on an opposite side of the stent sealing surface.
- the transducers are fixed to the tube by spacers (e.g. 32 / 132 and 33 / 133 ).
- the spacers support the transducers, such that a gap is defined between the transducer and the tube.
- the gap is in the range of 0.05 to 4 mm.
- the gap is in the range of 0.1 to 2.5 mm.
- the gap is filled by an acoustic fluid which flows within the enclosing transducer sleeve 22 / 122 / 222 / 322 / 822 , thereby cooling the transducer.
- At least one of stents 224 , 324 , 326 is replaceable by a balloon.
- the catheter for ultrasonic-driven bladder drug delivery comprises at least one balloon, at least one stent, or any combination thereof.
- the ultrasound transducer is between 100-400 Khz. In some embodiments, the ultrasound transducer is between 125-350 Khz. In some embodiments, the ultrasound transducer is between 150-300 Khz.
- the ultrasound transducer duty cycle is between 5-50%. In some embodiments, the ultrasound transducer duty cycle is between 7-45%. In some embodiments, the ultrasound transducer duty cycle is between 10-40%.
- the ultrasound Isppa intensity is between 5-60 W/cm2. In some embodiments, the ultrasound Isppa intensity is between 8-55 W/cm2. In some embodiments, the ultrasound Isppa intensity is between 10-50 W/cm2.
- the bladder distance from the ultrasound transducer ranges between 1-30 mm
- the total treatment time in which the transducer is in use ranges between 5-30 minutes. In some embodiments, the total treatment time in which the transducer is in use ranges between 10-25 minutes. In some embodiments, the total treatment time in which the transducer is in use ranges between 15-20 minutes.
- the acoustic fluid pressure ranges between 0.3 Mpa to 2 Mpa. In some embodiments, the acoustic fluid pressure ranges between 0.5 Mpa to 1 MPa.
- 3-40 mL of fluid fill up the volume of the transducer sleeve In some embodiments, 5-20 mL of fluid fill up the volume of the transducer sleeve. In some embodiments, 10-14 mL of fluid fill up the volume of the transducer sleeve.
- 5-300 mL of fluid is streamed into the bladder volume. In some embodiments, 15-100 mL of fluid is streamed into the bladder volume. In some embodiments, 25-50 mL of fluid is streamed into the bladder volume.
- Gas bubbles in liquid serve as nucleation seeds for the generation of cavitation. Therefore, increasing the amount of gas bubbles in the therapeutic fluid increases the efficiency of the ultrasound treatment.
- ultrasound transducers introduced into the bladder are commonly limited in the level of energy they can emit. Additionally, the fluid medium partially blocks and/or slows down ultrasound waves traveling from the transducer towards the bladder wall, thereby exposing the bladder wall to energy which may be insufficient for driving the treatment agent onto the tissue. Hence, to achieve efficacious treatment of a bladder wall, the ultrasound transducer needs to be activated in close proximity to the bladder wall, which increases the risk of damage to the wall tissue due to exposure to excessive heat generated from the transducer.
- nucleation seeds such as solid particles, semi-solids, micro-bubbles, and the like
- introduction of nucleation seeds, such as solid particles, semi-solids, micro-bubbles, and the like, in the therapeutic fluid distributes gas bubbles throughout the fluid.
- the gas bubbles closer to the transducer absorb a portion of the ultrasound radiation by forming cavitation, however the presence of gas bubbles throughout the treatment volume and especially in proximity to the bladder wall enables their activation (i.e., production of cavitation) even by the low energy ultrasound waves that would be ineffective in the absence of the nucleation seeds.
- Dispersing of the cavitation in the therapeutic fluid allows cavitation throughout the therapeutic fluid and not only in the layer encountered by ultrasound emitted waves in the immediate surroundings of the transducer sleeve.
- increasing the amount of cavitation bubbles within the therapeutic fluid liquid is prepared by adding gassed sterile liquid, such as saline within the therapeutic agent.
- the gas is at least one of air, helium, nitrogen, oxygen, or any combination thereof.
- the pressurizing of a sterile liquid with a gas is at a pressure of 8 to 30 atmospheres.
- the predetermined duration is between 0.5-2 hours. In some embodiments, the predetermined duration is 1 hour.
- the equilibrium of gases When adding the gassed liquid into the therapeutic fluid, the equilibrium of gases is swayed toward the therapeutic agent, thereby increasing the gas content therein. When it decompresses (as pressure is immediately released) within the therapeutic agent, the equilibrium of gases is swayed back towards the surrounding atmosphere and the excess gas is released in the form of small bubbles. These small bubbles serve as cavitation nucleation sites during the treatment.
- the therapeutic fluid is mixed into the gassed fluid.
- the gassed fluid is mixed into the therapeutic fluid.
- the gassed fluid is a diluent for the therapeutic fluid.
- FIG. 15 is an exemplary chart of parameters of implementation of a catheter for ultrasonic-driven treatment of a bladder, in accordance with some embodiments of the invention. the following experiment was tested on 8 pigs.
- the ultrasonic-driven treatment of the bladder by implementation of the catheter for ultrasonic-driven treatment of a bladder begins by application of local anesthesia to the bladder 1 .
- the catheter 10 is inserted at step 1400 into bladder 1 through a urethra 3 and the expandable portions 24 , 26 , and transducer sleeve 22 are expanded at step 1420 by inflating 10-15 mL.
- the bladder 1 is washed twice with saline by supplying at step 1440 saline and then draining the bladder 1 at step 1430 through therapeutic fluid port(s) 17 .
- the expandable portions 24 , 26 , and transducer sleeve 22 are fully inflated inside the bladder to 35 mL.
- a pump is started to circulate acoustic fluid within the expandable portions 24 , 26 , and transducer sleeve 22 .
- the transducer is switched on at a frequency of 200 kHz for 15 minutes, and turned off, as depicted by FIG. 15 .
- the duty cycle of the transduce is 15%.
- the therapeutic fluid is incubated within the bladder post-treatment for 10 minutes, as depicted by FIG. 15 .
- the therapeutic is botulinum toxin A (Botox®) solution in saline.
- the dose of the toxin is 100-200 units.
- the saline is normal sterile saline.
- the fluid is not gassed.
- FIG. 16 is a graph of the contractility of the detrusor muscle after each treatment: treatments using catheter for ultrasonic-driven treatment of a bladder compared to untreated tissue, and gold standard 100 units Botox® intravesical injections.
- the contractility of the detrusor muscle after each treatment as shown by the y-axis is a percent ratio of the contractility after a treatment in relation to the contractility of the detrusor muscle after receiving carbachol (CCh).
- CCh carbachol
- the contractility vs. CCh ratio depicts how much each detrusor muscle contracted in relation to a maximal contraction achieved by the CCh treatment.
- the bladders which received treatment using the catheter had a contractility vs. CCh ratio of about 39%, whereas the bladders which received the intravesical injections had a contractility vs. CCh ratio of about 44%, and the control group was at about 61%.
- the bladders which received treatment using the catheter had a contractility vs. CCh ratio of about 78%, whereas the bladders which received the intravesical injections had a contractility vs. CCh ratio of about 82%, and the control group was at 100%.
- FIG. 17 is a table of efficacy data from two human patients comparing pre-procedure bladder function to 14 days post procedure bladder function.
- the average volume of each micturation increased by 22% and 27% for patients 3002 and 3004 , respectively. Increase in the volume of each micturation is indicative of more urine filling up the bladder of the patient before urination. Additionally, the average number of nocturnal urinations has decreased by 60% and 10% for patients 3002 and 3004 , respectively, which corresponds to the increase in volume of each micturation. An increase in the volume of each micturation decreases the number of times a patient needs to urinate.
- the average number of urinary incontinence for patient 3004 decreased by 62.5%.
- patient 3002 experienced no change in the average number of urinary incontinence.
- the decrease of number of urinary incontinence shows the efficacy of the treatment using the catheter for ultrasonic-driven treatment in human patients suffering from OAB.
- range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.
- a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range.
- the phrases “ranging/ranges between” a first indicate number and a second indicate number and “ranging/ranges from” a first indicate number “to” a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals therebetween.
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Abstract
Description
-
- Inserting (as shown in
FIG. 4A ) acatheter 10 into bladder 1 through aurethra 3; - Expanding (
FIG. 4B )balloon 20, includingexpandable portions transducer sleeve 22, to a pre-determine pressure or volume by a pressurized acoustic fluid (e.g. 20 cc-40 cc of fluid) and keeping expandedportions 24/26 andtransducer sleeve 22 at an expanded state; - Draining the bladder 1 of fluid through therapeutic fluid port(s) 17;
- Supplying saline through therapeutic fluid port(s) 17;
- Mixing therapeutic fluid with gassed liquid as described elsewhere herein (this step can be performed any time prior or during the deployment of the catheter); and
- Supplying (
FIG. 4C ) a therapeutic fluid (e.g. 20-40 cc) into the bladder via therapeutic fluid port(s) 17. In some embodiments, such as depicted byarrow 400, therapeutic fluid is supplied via therapeutic fluid port(s) 17 into the bladder lumen.
- Inserting (as shown in
-
- Inserting at
step 1000 distalexpandable portion 26 ofcatheter 10 into bladder 1 throughurethra 3; - Removing at
step 1010 urine from the bladder via port(s) 17; - Expanding at
step 1020portion 26 to an expanded state by providing fluid intoportion 26 viaport 15; - Optionally, Mixing at
step 1030 therapeutic fluid with gassed liquid as described elsewhere herein (this step can be performed any time prior or during the deployment of the catheter); - Supplying at
step 1040 therapeutic fluid through the therapeutic fluid port(s) 17; - Further advancing at
step 1050 proximalexpandable portion 24 into bladder 1 throughurethra 3; and - Expanding at
step 1060 proximalexpandable portion 24 to an expanded state by providing fluid viaport 14.
- Inserting at
-
- Fixing
catheter 10 within the bladder 1 by ensuring the expandedballoon portion 24 engages theproximal surface 5 of the bladder 1; - Circulating at
step 1070 the acoustic fluid within thetransducer portion 22 by providing acoustic fluid via a firstfluid port 15 and extracting acoustic fluid via a secondfluid port 14; - Activating at
step 1080 thetransducer 30; and - Forming at
step 1090 cavitation in the therapeutic fluid inside the bladder treatment volume.
- Fixing
-
- Inactivating
transducer 30; - Extracting therapeutic fluid through therapeutic fluid port(s) 17;
- Supplying saline through therapeutic fluid port(s) 17 (e.g. to clean the bladder); and
- Collapsing the expanded
portions acoustic fluid ports - Withdrawing
catheter 10 out of the bladder 1 viaurethra 3.
- Inactivating
-
- Inserting at
step 1400catheter 10 into bladder 1 through aurethra 3; - Removing at
step 1410 urine from the bladder 1 via port(s) 17; - Expanding at
step 1420expandable portions transducer sleeve 22, to a pre-determined pressure or volume by a pressurized acoustic fluid (e.g. 20-40 cc of fluid) and keeping expandedportions 24/26 andtransducer sleeve 22 at an expanded state; and - Optionally, draining at
step 1430 the bladder of fluid through therapeutic fluid port(s) 17. - In some embodiments of the invention and as further shown in
FIG. 7 , deployment of the catheter is followed by a method of treatment of the bladder comprising: - Supplying at
step 1440 saline through therapeutic fluid port(s) 17; - Supplying at
step 1450 an optionally gassed liquid as described elsewhere herein through bladder therapeutic fluid port(s) 17; - Activating at
step 1460 thetransducer 30; - Inactivating at
step 1470transducer 30; - Draining at
step 1480 the bladder of the optionally gassed fluid through therapeutic fluid port(s) 17; - Supplying at step 1490 a therapeutic fluid (e.g. 20-40 cc) through therapeutic fluid port(s) 17.
- Inserting at
-
- deploying a catheter for ultrasonic-driven treatment of a bladder wall in a bladder;
- supplying therapeutic fluid (e.g., Botox®) into the bladder;
- forming cavitations in the fluid within the bladder; and
- draining the bladder.
-
- deploying a catheter for ultrasonic-driven treatment of a bladder wall in a bladder;
- supplying therapeutic fluid (e.g., Botox®) into the bladder;
- forming cavitations in the fluid within the bladder for a predetermined period of time followed by
- leaving the therapeutic fluid in the bladder for a predetermined period of time; and
- draining the bladder.
-
- supplying the bladder with gaseous fluid;
- forming cavitations in the gaseous fluid;
- draining the gaseous fluid; and
- supplying the bladder with therapeutic fluid.
-
- deploying a catheter for ultrasonic-driven treatment of a bladder wall in a bladder;
- supplying the bladder with gaseous therapeutic fluid;
- forming cavitation in the gaseous fluid for a predetermined period of time;
- followed by
- draining the bladder.
-
- Inserting
catheter 110 intobladder 100 throughurethra 103 until thedistal end 117 engages the bladder distal (opposing the trigone)internal surface 105; - Expanding
balloon 124 and thetransducer sleeve 122 to a pre-determined pressure or volume by a pressurized acoustic fluid and maintaining all expanded portions at an expanded state; - Draining the
bladder 100 through therapeutic fluid port(s) 116; - Washing the bladder by inserting saline and draining the saline through port(s) 116;
- Mixing therapeutic fluid with gassed liquid as described elsewhere herein (this step can be optional or performed any time prior or during the deployment of the catheter); and
- Providing a therapeutic fluid through therapeutic fluid port(s) 116.
- Inserting
-
- Fixing
catheter 110 withinbladder 100 by ensuring expandedballoon 124 engages the proximal wall (trigone area) 105′ of the bladder; - According to some embodiments of the invention, circulating the acoustic fluid within the
transducer portion 122 by supplying fluid via a firstfluid port 115 a and removing acoustic fluid via a secondfluid port 115 b; and - Activating the
transducer 130.
- Fixing
-
- Inactivating the operation of
transducer 130; - Removing therapeutic fluid via
therapeutic fluid ports 116; - Inserting saline on
bladder surface 105 through ports 116 (e.g. to clean the bladder). - Collapsing expanded
portions acoustic fluid ports - Withdrawing
catheter 110 out of thebladder 100 throughurethra 103.
- Inactivating the operation of
-
- Inserting
catheter 110 intobladder 100 through aurethra 103; - Expanding
balloon 124 and thetransducer sleeve 122, to a pre-determine pressure or volume by a pressurized acoustic fluid (e.g. 20-40 cc of fluid) and keeping expandedballoon 124 andtransducer sleeve 122 at an expanded state; - Draining the bladder of fluid through therapeutic fluid port(s) 116;
- Supplying saline through therapeutic fluid port(s) 116;
- Supplying a gassed liquid as described elsewhere herein through bladder therapeutic fluid port(s) 116;
- Activating the
transducer 130; -
Inactivating transducer 130; - Draining the
bladder 100 of gassed fluid through therapeutic fluid port(s) 116; - Supplying a therapeutic fluid (e.g. 20-40 cc) through therapeutic fluid port(s) 116.
- Inserting
-
- pressurizing a sterile liquid with a gas to generate a gassed liquid;
- maintaining the gassed liquid compressed for a predetermined duration;
- preparing a therapeutic fluid by releasing a therapeutic agent (formed as a powder or a liquid) into the gassed liquid.
Claims (15)
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US17/044,184 US11529506B2 (en) | 2018-04-01 | 2019-04-01 | System and method for ultrasonic bladder therapeutic agent delivery |
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US17/044,184 US11529506B2 (en) | 2018-04-01 | 2019-04-01 | System and method for ultrasonic bladder therapeutic agent delivery |
PCT/IL2019/050378 WO2019193591A1 (en) | 2018-04-01 | 2019-04-01 | System and method for ultrasonic bladder therapeutic agent delivery |
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US11045128B2 (en) | 2017-06-03 | 2021-06-29 | Sentinel Medical Technologies, LLC | Catheter for monitoring intra-abdominal pressure |
US11672457B2 (en) | 2018-11-24 | 2023-06-13 | Sentinel Medical Technologies, Llc. | Catheter for monitoring pressure |
US11779263B2 (en) | 2019-02-08 | 2023-10-10 | Sentinel Medical Technologies, Llc. | Catheter for monitoring intra-abdominal pressure for assessing preeclampsia |
US20220142806A1 (en) * | 2019-05-17 | 2022-05-12 | Nxt Biomedical, Llc | Urine Collecting System Interventions For Improving Kidney Function |
EP4009860A4 (en) | 2019-08-08 | 2022-11-16 | Sentinel Medical Technologies, LLC | Cable for use with pressure monitoring catheters |
US11617543B2 (en) * | 2019-12-30 | 2023-04-04 | Sentinel Medical Technologies, Llc. | Catheter for monitoring pressure |
WO2022212416A1 (en) * | 2021-03-31 | 2022-10-06 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and systems for treatment of occlusions in anatomical cavities using acoustic wave energy |
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US20210052873A1 (en) | 2021-02-25 |
AU2019249430B2 (en) | 2024-05-02 |
EP3773262A1 (en) | 2021-02-17 |
AU2019249430A1 (en) | 2020-10-22 |
CN112261912A (en) | 2021-01-22 |
EP3773262A4 (en) | 2022-01-19 |
JP2021519671A (en) | 2021-08-12 |
CA3095598A1 (en) | 2019-10-10 |
US20230097230A1 (en) | 2023-03-30 |
JP7384894B2 (en) | 2023-11-21 |
IL277675A (en) | 2020-11-30 |
WO2019193591A1 (en) | 2019-10-10 |
KR20210005588A (en) | 2021-01-14 |
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